Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00091117
First received: September 7, 2004
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. This phase I trial is studying the side effects and best dose of bortezomib in treating patients with advanced cancer and liver dysfunction.


Condition Intervention Phase
Hepatic Complications
Malignant Neoplasm
Drug: bortezomib
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEPSponsored Organ Dysfunction Working Group

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • DLT [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • MTD [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Enrollment: 80
Study Start Date: July 2004
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction.

II. Determine the safety and tolerability of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients with mild, moderate, or severe liver insufficiency.

IV. Examine the dietary influences on bortezomib disposition and efficacy. V. Examine the influences of proteasome inhibition on CYP 450 activity.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients per stratum receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

[Note: Patients with normal hepatic function do not receive escalating doses of bortezomib.]

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed malignancy for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
  • Tumor types may include any of the following: solid tumors:

    • Non-Hodgkin's lymphoma
    • Hepatocellular carcinoma, as evidenced by liver mass, elevated alpha-fetoprotein level (>= 500 ng/mL), and positive serology for hepatitis
  • Pathological confirmation is not required
  • Confirmatory evidence for a prior Hepatitis B infection (HBsAg, HBcAb and/or HBsAb) required
  • No symptomatic CNS metastases
  • Brain metastasis allowed if the following criteria are met:

    • Received prior definitive treatment (radiation and/or surgery
    • Stable disease for >= 4 weeks
    • Not currently on enzyme-inducing anticonvulsants and steroids
  • Life expectancy of at least 12 weeks
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Biliary obstruction for which a shunt has been placed allowed provided the shunt has been in place for >= 10 days AND liver function is stable, defined as 2 measurements taken >= 2 days apart that qualify the patient for the same hepatic dysfunction stratum
  • No biliary sepsis
  • Creatinine =< 1.5 mg/dL
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No New York Heart Association class III or IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • No preexisting neuropathy >= grade 2
  • No ongoing or active infection
  • No other concurrent uncontrolled illness that would preclude study participation
  • No psychiatric illness or social situation that would preclude study compliance
  • More than 4 weeks since prior immunotherapy
  • More than 4 weeks since prior biologic therapy
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent immunotherapy
  • No concurrent thalidomide
  • Concurrent epoetin alfa or darbepoetin alfa for management of cancer-associated anemia allowed
  • Recovered from prior chemotherapy (not including liver function)
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No concurrent chemotherapy
  • More than 2 weeks since prior radiotherapy
  • No prior radiotherapy to > 50% of the bone marrow
  • No concurrent radiotherapy
  • More than 3 weeks since prior surgery
  • No prior bortezomib
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • Concurrent cytochrome P450 interacting agents are allowed provided they are used with caution
  • Concurrent bisphosphonate therapy allowed (e.g., pamidronate or zoledronate), except during course 1 of bortezomib administration
  • ECOG 0-2
  • Fertile patients must use effective contraception during and for 30 days after study participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091117

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
Investigators
Principal Investigator: Patricia LoRusso Wayne State University
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00091117     History of Changes
Other Study ID Numbers: NCI-2009-00059, NCI-2009-00059, CDR0000383782, C-2802, C-2802, 6432, U01CA062487, U01CA062505, U01CA069853, U01CA062491, U01CA070095
Study First Received: September 7, 2004
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014